Case Study: Cardiovascular Physiology Learning Outcomes: Apply physiological and
ID: 3522600 • Letter: C
Question
Case Study: Cardiovascular Physiology
Learning Outcomes:
Apply physiological and biochemical knowledge to analyze case studies on pathological states.
Communicate biological information effectively in written work.
Apply physiology to relevant societal impacts.
Kristopher is a retired United States Marine. He has a history of physical activity and no major health problems prior to this visit. He complains that he has recently been having palpitations, light-headedness, and breathlessness after exercise. He recently fainted after trying to run a half-marathon. He has no family medical history as he was adopted. The doctor orders a series of test including a stress test (monitors the heart activity during exercise). During the test Kristopher suffered from sudden cardiac death. An autopsy revealed altered heart muscle structures with fatty deposits and scar tissue formation. Genetic analysis of the tissue indicated altered plakophilin2 levels. The levels of this protein were significantly decreased.
QUESTION: Recent studies suggest that plakophilin 2 may be required for proper transcription of genes controlling intracellular calcium cycling, which may, in turn, disrupt intracellular calcium homeostasis. Even in the absence of structural disease, why may this affect normal human physiology?
Explanation / Answer
Plakophilin-2 (PKP2) role in cell-cell adhesion. Mutations in human PKP2 relate with a life-threatening arrhythmogenic cardiomyopathy, frequently right ventricular predominance. PKP2 is necessary to maintain transcription of genes that control intracellular calcium cycling. Lack of PKP2 reduces expression of:- Ryr2 (coding for Ryanodine Receptor 2), Ank2 (coding for Ankyrin-B), Cacna1c (coding for CaV1.2), Trdn (coding for triadin), protein levels of calsequestrin-2 (Casq2). These factors combined lead to disruption of intracellular calcium homeostasis and isoproterenol-induced arrhythmias PKP2 expression suggest that mutations in PKP2 in humans may cause life-threatening arrhythmias even in the absence of structural disease.It is assume that mutations in plakophilin 2 (PKP2) protein cause arrhythmia due to loss of cell-cell communication. The calcium cycle involve in human hearts PKP2 protein can controls the expression of this cycle due to the lack of PKP2 protein can cause arrhythmia in a structurally normal human.